High contrast imaging of low boiling point phase change contrast agents in moving tissue with ultrafast inter-frame activation imaging sequence

Nanoscale phase change contrast agents (PCCA) have been demonstrated for extravascular imaging in tissue. However, contrast in PCCA images is typically limited by physiological motion and incomplete cancelation of unwanted tissue signal. In this work, we develop an ultrafast inter-frame activation imaging sequence for high contrast PCCA imaging in the presence of physiological motion by imaging the inter-frame variation produced by activation of PCCA, which is distinguishable from tissue and blood motion. Phantom studies indicate that in the absence of tissue motion, the CTR of UIAU images is 19.55±0.42 dB while the CTR of the amplitude modulate + pulse inversion (AMPI) is 8.15±0.65 dB and the CTR of differential imaging is 24.20±1.22 dB. Furthermore, the CTR of these UIAU images can reach 51.43±3.3 dB by applying a denoising approach. With 20 mm/s motion, the CTR of UIAU and denoised UIAU images were 18.70±1.40 dB and 31.77±9.76 dB respectively, which were both significantly higher than that of amplitude modulation + pulse inversion (AMPI) and differential images. The preliminary in vivo imaging results indicate the UIAU could significantly suppress the background tissue in the presence of physiological motion.